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EC number: 932-161-6 | CAS number: -
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
![](https://chesar.echa.europa.eu/o/diss-blank-theme/images/factsheets/A-REACH/factsheet/print_toxicological-information.png)
Repeated dose toxicity: oral
Administrative data
- Endpoint:
- sub-chronic toxicity: oral
- Type of information:
- migrated information: read-across based on grouping of substances (category approach)
- Adequacy of study:
- key study
- Study period:
- 15 Jul - 15 Oct 2002
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: GLP guideline study.
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 003
- Report date:
- 2003
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Remarks:
- Inspectorate for Health Protection, Commodities and Veterinary Public Health; Ministry of Health, Welfare and Sport; The Netherlands.
- Limit test:
- no
Test material
- Reference substance name:
- Vinasses, residue of fermentation
- EC Number:
- 932-215-9
- Molecular formula:
- Not applicable (a generic molecular formula cannot be provided for this specific UVCB substance).
- IUPAC Name:
- Vinasses, residue of fermentation
- Details on test material:
- - Name of test material (as cited in study report): Sirional E. Coli (LYS + THR), (Liquid by product from the production of lysine and threonine by E. Coli K12)
- Physical state: Dark brown viscous liquid
- Analytical purity: Not relevant (complex mixture used as feed material)
- Lot/batch No.: Not given (only one batch was produced; CP trial 13/14 November 2001)
- Expiration date of the lot/batch: 12 April 2004
- Storage condition of test material: 2-10 "C, in a dry place
- Composition
dry matter: 61.14%, water: 38.86%, total nitrogen: 6.22%, crude proteins: 38.87%, ammoniacal nitrogen: 4.18%
pH (solution 10%) 4.4, ashes: 2.78%, K: 0.17%, Na: 0.87%, Ca: n.d., Mg: n.d., Cl: 0.375%, SO4: 14.23%, P: 0.12%
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Wistar
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany
- Weight at study initiation: 174.8-215.8 g (males), 126.7-156.9 g (females)
- Age at study initiation: approx. 7 weeks
- Fasting period before study: no
- Diet (ad libitum): AIN-93G control diet from 4 days before study initiation on
- Water: ad libitum
- Acclimation period: the animals were delivered approximately 2 weeks before the start of the study
IN-LIFE DATES: 03 July 2002 - 15 Oct 2002
Administration / exposure
- Route of administration:
- oral: feed
- Vehicle:
- other: plain diet
- Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Integrity of the test diets
In the first batch of test diets the following analyses were performed:
- dry matter (TNO SOP DASlLNCl069);
- crude protein (TNO SOPS LNCIlO1 en LNC102);
- crude fat (TNO SOP LNCl139);
- crude fibre (TNO SOP DASlLNCIO11);
- ash (TNO SOP DAS/LNCl131);
- Ca, P, Na, K (TNO SOP DAMlLSPl057);
- Cl (TNO SOP LNCl216). - Duration of treatment / exposure:
- 13 weeks of dosing
- Frequency of treatment:
- daily ad libitum
Doses / concentrationsopen allclose all
- Remarks:
- Doses / Concentrations:
0, 2, 6 and 15%
Basis:
nominal in diet
- Remarks:
- Doses / Concentrations:
0, 1000, 3000 and 8000 mg/kg bw /day
Basis:
other: mean test substance intakes (approx.) in males
- Remarks:
- Doses / Concentrations:
0, 1200, 3300, 9600 mg/kg bw /day
Basis:
other: mean test substance intakes (approx.) in females
- No. of animals per sex per dose:
- 10
- Control animals:
- yes, plain diet
- other: additional ammonium (derived from (NH4)2S04); approx. 0.6%) control group
- Positive control:
- 0.6% ammonium (derived from (NH4)2S04)
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: daily
BODY WEIGHT: Yes
- Time schedule for examinations: At initiation of treatment and once weekly thereafter
FOOD CONSUMPTION: Yes
- Time schedule for examinations: 3- or 4-day periods, measured by cage
FOOD EFFICIENCY:
- The intake of test substance per kg body weight per day was calculated from the nominal dietary concentration of the test substance, the food consumption and the mean body weight in the period for which the intake of test substance is calculated.
WATER CONSUMPTION: Yes
- Time schedule for examinations: 4-day periods in weeks 1,6 and 12
FAECES COLLECTION: Yes
- Time schedule for examinations: In weeks 2, 7 and 13
NEUROBEHAVIOURAL EXAMINATION: Yes
- Time schedule for examinations: Prior to the first exposure and then once weekly up to and including week 11. S
- Dose groups that were examined: All animals
- Battery of functions tested: spontaneous motor activity measurements and Functional Observational Battery (FOB) tests were performed towards the end of the study (week 12/13).
OPHTHALMOSCOPIC EXAMINATION: Yes
- Time schedule for examinations / Dose groups that were examined: Prior to the start of treatment in all animals and towards the end of the treatment period in all surviving animals of the control groups and the high-dose group.
HAEMATOLOGY: Yes
- Time schedule for collection of blood: At necropsy at the end of treatment
- Anaesthetic used for blood collection: CO2/O2
- Animals fasted: Yes
- How many animals: all animals
- Parameters examined: haemoglobin, packed cell volume, red blood cell count, reticulocytes, total white blood cell count, differential white blood cell count, prothrombin time, thrombocyte count
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: At necropsy at the end of treatment
- Animals fasted: Yes
- How many animals: all animals
- Parameters examined: alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, gamma glutamyl transferase, total protein, albumin ratio albumin to globulin, urea, creatinine, fasting glucose, bilirubin (total), cholesterol (total), triglycerides, phospholipids, Ca, Na, K, Cl, inorganic phosphate
RENAL CONCENTRATION TEST:
- Time schedule for collection of blood: Shortly before the end of the treatment (days 87-88)
URINALYSIS: Yes
- Time schedule for collection of urine: Shortly before the end of the treatment (days 87-88)
- Metabolism cages used for collection of urine: Yes
- Animals fasted: Yes
- Parameters examined: appearance, glucose, pH, occult blood, ketones, protein, bilirubin, urobilinogen, microscopy of the sediment - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes
All animals were subjected to a complete gross necropsy. In week 14, after overnight fasting, the surviving animals were killed. A thorough autopsy was also performed on the animal that had to be killed because it was moribund. At final necropsy, the following organs were weighed (paired organs together) as soon as possible after dissection to avoid drying: Adrenals, ovaries, brain, spleen, epididymides, testes, heart, thymus, kidneys, thyroid (with parathyroids), liver and uterus.
Samples of the following tissues and organs of all animals were preserved in a neutral aqueous phosphate-buffered 4 per cent solution of formaldehyde:
Adrenals, parathyroid, aorta, * parotid salivary glands, axillary lymph nodes pituitary, brain (brain stem, cerebrum, cerebellum), prostate, caecum, rectum, colon * seminal vesicles with coagulating glands, epididymides, skeletal muscle (thigh),* exorbital lachrymal glands, skin (flank), eyes, small intestine (duodenum, ileum, jejunum), femur with joint spinal cord (at three levels), GALT (gut associated lymphoid tissue including Peyer's patches), sternum with bone marrow, stomach (glandular and non-glandular), heart, sublingual salivary glands, kidneys, submaxillary salivary glands, liver, testes, lungs, thymus, mammary gland (females), thyroid, * mandibular (cervical) lymph nodes, trachea/bronchi, mesenteric lymph nodes, urinary bladder, nerve-peripheral (sciatic), uterus (with cervix), oesophagus, * vagina, ovaries, pancreas, all gross lesions.
* The tissues marked with an asterisk were preserved but not processed for histopathological examination, since histopathological examination was not considered necessary on the basis of the results of gross observations.
Histopathological examination was performed on all tissues and organs listed above - except those marked with an asterisk - of all animals of the control groups (groups A and B) and of the high-dose group (group E), and of the animal that was killed in extremis. In addition, the lungs, liver, kidneys and gross lesions were examined microscopically in all rats of the intermediate dose-groups. - Other examinations:
- ORGAN WEIGHTS: adrenals, brain, epididymides, heart, kidneys, liver, ovaries, spleen, testes, thymus, thyroid (with parathyroids), uterus
SPERM ANALYSIS AND ESTRUS CYCLE - Statistics:
- The statistical procedures used in the evaluation of data were as follows:
- body weight: one-way analysis of covariance (covariate: body weight on day 0) followed by
Dunnett's multiple comparison tests;
- red blood cell and clotting potential variables, total white blood cell counts, absolute differential
white blood cell counts, clinical chemistry values, volume and density of the urine, organ
weights: one-way analysis of variance (ANOVA) followed by Dunnett's multiple comparison
tests;
- food and water consumption and food efficiency: one-way analysis of variance (ANOVA) followed
by L.S.D. tests;
- reticulocytes, relative differential white blood cell counts, urinary parameters except for volume
and density: Kruskal-Wallis non-parametric ANOVA followed by Mann-Whitney U-tests;
- histopathological changes: Fisher's exact probability test;
- neurobehavioural observations: parameters assessed during functional observations were
measured on different measurement scales (e.g., continuous, rank, categorical). Functional
observational battery and motor activity results: one-way analysis of variance (Anova) followed
by Dunnett's multiple comparison tests (e.g. continuous and motor activity data),
Kruskal-Wallis non-parametric Anova followed by multiple comparison tests (rank order), or
Pearson chi-square test (categorical data);
- Sperm parameters were evaluated by ANOVA followed by Dunnett's multiple comparison tests
or Kruskal-Wallis non-parametric ANOVA followed by Mann-Whitney U-tests;
TNO report V46 1 9/04
July 2003
- Estrus cyclicity was evaluated by Fisher's exact probability test or ANOVA followed by
Dunnett's multiple comparison tests.
All tests were two-sided. Probability values of pC0.05 were considered significant.
Results and discussion
Results of examinations
- Details on results:
- CLINICAL SIGNS AND MORTALITY: No effects
BODY WEIGHT AND WEIGHT GAIN:
A slight reduction in growth and slightly reduced food consumption (during the first week of the study) were observed in the high-dose group, which were probably related to the high level of ammonium nitrogen in the test substance.
FOOD CONSUMPTION AND COMPOUND INTAKE:
The overall intake of Sirional E. Coli (LYS + THR) for the low-, mid-, and high-dose groups was approximately 1000, 3000 and 8000 mg/kg bw/d in males and 1200, 3300 and 9600 mg/kg bw/d in females, respectively. The intake of ammonium for the ammonium-control group was approximately 320 and 380 mg/kg bw/d in males and females, respectively.
WATER CONSUMPTION:
Water consumption was generally increased in a dose-related manner in males and females.
NEUROBEHAVIOUR: No effects
OPHTHALMOSCOPIC EXAMINATION: No effects
HAEMATOLOGY: No effects
CLINICAL CHEMISTRY:
Clinical chemistry parameters were generally similar among the groups. However, albumin was decreased in females of the ammonium-control group and of the high-dose group and the albumin/globulin ratio was decreased in males of the ammonium-control group and in females of the high-dose group. These changes were probably related to the high level of ammonium nitrogen in the test substance. The decrease in chloride in females of the high-dose group was considered treatment-related.
URINALYSIS:
Urinary density was increased in males of the ammonium-control group. Urinary volume and density were similar among the treated groups. Urinary pH was lower and urinary crystals were increased in males of the ammonium-control group and of the high dose group. These changes were considered related to the high level of ammonium nitrogen in the test substance.
ORGAN WEIGHTS:
Relative kidney weights were increased in the ammonium-control group (males) and in the high-dose group (males and females). Absolute brain weights were increased in females of the ammonium-control group and of the low- and high-dose groups. Relative brain weights were increased in the ammonium-control group (males) and in the high-dose group (males and females). Relative liver weights were increased in males and females of the high-dose group. Relative testes weights were increased in the ammonium-control group and in the mid-dose group. Absolute and relative uterus weights were increased in the low-dose group. All changes were considered either chance findings or related to the ammonium- level in the test substance, except for the change in relative liver weights, which was considered treatment-related.
GROSS PATHOLOGY: Macroscopic examination at autopsy did not reveal treatment-related gross changes. All lesions observed were about equally distributed amongst the controls and the different test groups, or they occurred in one or a few animals only.
HISTOPATHOLOGY: Microscopic examination revealed a statistically significant decrease in the incidence of microvesicular hepatocellular vacuolation in males of the high-dose group only. This histopathological lesion is not considered to be related to treatment, since a large variation in incidence of this condition is not uncommon in animals of this strain and age. All other lesions were about equally distributed between the controls and the different test groups, or they occurred in a single animal only.
FERTILITY PARAMETERS: No effects of the test substances on estrous cyclicity, epididymal sperm motility, epididymal sperm count, daily sperm production and sperm morphology were observed.
Effect levels
open allclose all
- Dose descriptor:
- NOAEL
- Effect level:
- 3 000 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male
- Basis for effect level:
- other: equivalent to 6% in the diet. No obvious signs of toxicity.
- Dose descriptor:
- NOAEL
- Effect level:
- 3 300 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- female
- Basis for effect level:
- other: equivalent to 6% in the diet. No obvious signs of toxicity.
Target system / organ toxicity
- Critical effects observed:
- not specified
Applicant's summary and conclusion
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.
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